Compounds isolated from a marine sponge include manoalide of the formula ##STR1## and seco-manoalide, of the formula ##STR2## These compounds were disclosed by de Silva, E. D., et al, Tet Lett (1981) 22: 3147-3150 and Tet Lett (1980) 21: 1611-1614. The anti-inflammatory and immunosuppressive activities of these compounds, and of an analog arising as an artifact of isolation, dehydroseco-manoalide ##STR3## are disclosed in U.S. Pat. No. 4,447,445, application for which was filed on even date with U.S. Ser. No. 519,853.
The present invention relates to synthetic analogs of manoalide which have anti-inflammatory activities in the same range as that of manoalide, i.e., greater than that of indomethacin and less than that of hydrocortisone. Uses include treatment of rheumatoid arthritis, osteoarthritis, rheumatic carditis, autoimmune diseases such as myasthenia gravis, allergic diseases, bronchial asthma and ocular and skin inflammatory diseases. These drugs are also useful as adjuvant therapy associated with organ and tissue transplants and, because they inhibit phospholipase A.sub.2, as a local treatment for any venom in which a major constituent is the enzyme phospholipase A.sub.2. In addition, manoalide analogs are immunosuppressants by virtue of their capacity to inhibit phospholipase A.sub.2. Since manoalide analogs block oxazolone-induced inflammation, these compounds are useful in treating forms of allergic contact dermatitis (such as poison oak or poison ivy). They are also antiproliferative agents.